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Neutrophilic asthma is steroid\u2010resistant and characterized by the absence or suppression of the T\u2010helper type II (T<jats:sub>H<\/jats:sub>2) process and an increase in the T<jats:sub>H<\/jats:sub>1 and\/or T<jats:sub>H<\/jats:sub>17 process. Roflumilast (ROF) has anti\u2010inflammatory effects and has been used to treat chronic inflammatory airway diseases, such as chronic pulmonary obstructive disease. It is unclear whether ROF may have a therapeutic role in neutrophilic asthma. In this study, we investigated the synergistic effect of ROF with dexamethasone (DEX) in a neutrophilic asthma mouse model. C57BL\/6 female mice sensitized to ovalbumin (OVA) were exposed to five intranasal OVA treatments and three intranasal lipopolysaccharide (LPS) treatments for an additional 10\u00a0days. During the intranasal OVA challenge, ROF was administrated orally, and DEX was injected intraperitoneally. Protein, pro\u2010inflammatory cytokines, inflammatory cytokines and other suspected markers were identified by enzyme\u2010linked immunosorbent assay, real\u2010time polymerase chain reaction, and western blot. Following exposure to LPS in OVA\u2010induced asthmatic mice, neutrophil predominant airway inflammation rather than eosinophil predominant inflammation was observed, with increases in airway hyperresponsiveness (AHR). The lungs of animals treated with ROF exhibited less airway inflammation and hyperresponsiveness. To investigate the mechanism underlying this effect, we examined the expression of proinflammatory cytokines suspected to be involved in inflammatory cytokines and proteins. Roflumilast reduced total protein in bronchioalveolar lavage fluid; levels of interleukin (IL)\u201017A, IL\u20101\u03b2 messenger RNA, interferon \u03b3 and tumour necrosis factor \u03b1; and recovered histone deacetylase\u20102 (HDAC2) activity. Combination therapy with ROF and DEX further reduced the levels of IL\u201017, IL\u201022 and IL\u20101\u03b2 mRNA and proinflammatory cytokines. The combination of ROF and DEX reduced lung inflammation and AHR much more than one of them alone. Roflumilast reduces AHR and lung inflammation in the neutrophilic asthma mouse model. Furthermore, additive effects were observed when DEX was added to ROF treatment, possibly because of recovery of HDAC2\/\u03b2\u2010actin activity. This study demonstrates the anti\u2010inflammatory properties of ROF in a neutrophilic asthma mouse model.<\/jats:p>","DOI":"10.1111\/1440-1681.13635","type":"journal-article","created":{"date-parts":[[2022,2,19]],"date-time":"2022-02-19T06:29:15Z","timestamp":1645252155000},"page":"624-632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synergistic effect of roflumilast with dexamethasone in a neutrophilic asthma mouse model"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4107-444X","authenticated-orcid":false,"given":"Chan Kwon","family":"Park","sequence":"first","affiliation":[{"name":"Division of Pulmonology, Allergy and Critical Care Medicine Department of Internal Medicine Yeouido St. Mary's Hospital College of Medicine The Catholic University of Korea Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai 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